The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

Osteonecrosis of the jaw and bisphosphonates.

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Brentuximab Vedotin and Pembrolizumab Combination in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Single-Centre Retrospective Analysis

Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

L'anémie de la personne âgée

Anaemia is a problem that affects almost 10 % over 65 years and 20 % over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia ;anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).SCOPUS: ar.jinfo:eu-repo/semantics/publishe

THE 4TH LYSA MEETING

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New therapeutic approaches in cutaneous T-cell lymphomas.

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Anémie hémolytique et syndrome dysentérique :à propos d'un cas de rectocolite ulcéro-hémorragique

A 53-years-old man has a dysentery since two weeks. The blood test shows Coombs-positive hemolytic anemia and inflammation. Autoimmune hemolytic anemia (AIHA) is treated with corticosteroid. A colonoscopy reveals an ulcerative colitis. The evolution of the patient is complicated by a spontaneous digestive perforation treated by total proctocolectomy. After this intervention, there is a resolution of the AIHA and the patient is gradually weaned from corticosteroids. AIHA is a rare extra-intestinal manifestation of inflammatory bowel disease essentially ulcerative colitis. Identification of this cause of secondary AIHA is important for the therapeutic strategy. However treatment is nonspecific and based on low levels of evidence.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Early Discontinuation of Lenalidomide in Patients with Relapsing or Refractory Multiple Myeloma: Predictive Factors for Stopping in the Real Life

Abstract Introduction: The immunomodulatory drug lenalidomide (Len) is a major drug in myeloma treatment. It has been reported that continuous treatment with Len until disease progression or unacceptable toxicity is associated with a better outcome. Although an early Len stop is associated with a decrease of progression free survival and overall survival, there is few published data on the reasons of early discontinuation beside disease progression. The aim of this study is to evaluate, in the real life, the reason of early Len discontinuation in patients with relapsed or refractory multiple myeloma. Methods: We retrospectively reviewed relapsing or refractory myeloma patients who received a Len based treatment in our center from January 2008 to December 2015. We collected data on toxicity, treatment discontinuation and dose modifications from the start of Len therapy until treatment discontinuation. We analyzed the baseline characteristics of the patients and their treatment. Results: 78 patients received a Len therapy for a total of 107 lines of treatment. The median age was 62 (38-84) years. The treatment was a combination of Len and low dose dexamethasone (dex) in 71% of the cases (n=75) and a triple combination in 29% (n=32) including a majority of Len-dex-cyclophosphamide (n=17) and Len-dex-bortezomib (n=12). The treatment was discontinued for toxicity in 39% (n=34) of the patients. Main reasons for early discontinuation of Len were: hematological toxicity in 38% (n=13), general symptoms (malaise, asthenia) in 32% (n=11), gastro intestinal toxicity in 9% (n=3). 47% of the pts (n=16) stopped treatment due to more than one toxicity. The median duration of treatment was 5.8 months for patients stopping Len for toxicity reasons compared to 11, 7 months in patients stopping Len for disease progression. Discontinuation for hematological toxicities was usually preceded by dose reduction. In a multivariate analysis, predictive factors for early Len discontinuation were: age (OR :1,08 (1,03 - 1,11) ;p = 0,004) and a triple combination (OR :4,84 (1,71 - 13,71) ;p = 0,003). Receiver operating characteristic (ROC) curves identified an age threshold of 69 predictive of early arrest for another cause than progression with an area under the ROC curves of 0,67 (0,55 - 0,79). The presence of comorbidities was not associated with a risk of dose reduction or early arrest of therapy. A reduction of the Len dose was done in 31% of the 107 lines (n=33). In 81 % of these 33 lines, we observed ≥ 2 toxicities (median of 3; range 1-9). The most frequently reported toxicities were: general symptoms in 84% (n=27), GI toxicity in 53% (n=17), infection in 13%. Hematological toxicity was reported in 87% although it motivated a dose reduction in only 22% of the lines (n=7). The only predictive factor for dose reduction in multivariate analysis was sex (OR :3,63 (1,37 - 10,59) ;p = 0,007) with 76% of dose reduction in males comparing to 24% in females. In 75% of the cases (n=29) the dose reduction was followed by an early discontinuation of treatment for toxicity. Conclusion In our survey, Len-related non hematological toxicity is observed more frequently than expected from the literature and Len therapy modification was frequently due to multiple toxicities. In our analysis, age and Len-dex based triple combination are predictive factors for early Len discontinuation. Sex was a predictive factor for Len dose reduction. This has previously not been reported and may be due to the small sample size of this study. On the other hand this may be explained by variable pharmacokinetics in male and female. Interestingly, a dose reduction was followed in 75% of the cases by an early discontinuation of Len suggesting that - in patients at high risk of discontinuation of Len (e.g. older males) - Len could be started at lower dose and progressively increased according to the tolerance. Disclosures Meuleman: Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy; Amgen: Consultancy; Celgene: Consultancy.info:eu-repo/semantics/publishe